Measurement of blood flow, in vivo, is important for the functional assessment of the circulatory system. Angiography has become a standard technique for making such functional assessments. Typically, an arterial catheterization is performed on a subject, for whom an angiograph is to be prepared, wherein a so-called "contrast agent" or iodinated contrast agent is introduced, after which radiographic imaging is performed.
Radiographic imaging of the body is well known and extremely useful as a diagnostic tool in the medical arts. Radiographic imaging involves positioning a part of a patient to be imaged denoted as the "structure of interest" under an X-ray tube, exposing the structure of interest to an X-ray beam, and recording the X-ray image on an image receptor. The receptor in most instances is a radiographic film disposed in contact with an intensifying screen. The intensifying screen absorbs x-ray radiation and radiates light in proportion to the radiation absorbed. Light emitted by the intensifying screen exposes the film. In an angiograph, the contrast agent causes highlights on the developed film of that portion of the circulatory system through which the contrast agent is flowing or highlights that organ or group of organs into Which the contrast agent has been ingested.
The problem with such previous angiographic techniques is the reliance on the administration of exogenous tracers, and such techniques may require arterial blood sampling for quantitation.
In recent years, there has been suggested the use of magnetic resonance imaging (MRI) techniques to produce angiographic like images. Such applications of MRI have been referred to as magnetic resonance angiography (MRA). MRA has the potential to provide detailed angiographic images of the human body. Additionally, MRA is non-invasive, with flow induced contrast substituting for iodinated contrast media. In order to appreciate MRA, a general summary of magnetic resonance techniques is appropriate.
Magnetic resonance (MR) is defined as the enhanced absorption of energy occurring when the nuclei of atoms or molecules within an external magnetic field are exposed to radio frequency (RF) energy at a specific frequency, called the Larmor or resonance frequency. Drs. Bloch and Purcell each received the Noble Prize for investigating and describing in 1946 the phenomenon of MR in solids and liquids. The characteristics of the MR signal arising from a given nucleus were found to depend on a specific molecular environment of that nucleus and such signal dependence proved ideal for qualitative and quantitative chemical analysis. Moreover, the radio frequencies involved in MR are non-ionizing and can penetrate the human body.
Although MR suggested enormous clinical potential for in vivo studies, the potential of the method was limited by its inability to provide spatial localization of the MR signal. Lauterbur resolved the localization problem through the use of magnetic field gradients. Since 1977, various MR techniques have been developed for the generation of two and three dimensional data of a human subject.
The production of an MR image can be generally summarized by the following steps. Randomly oriented nuclei are aligned by a powerful uniform magnetic field. This alignment of magnetization is disrupted by properly tuned RF pulses. These pulses disrupt or perturb the nuclei alignment. As the nuclei recover their alignment, they undergo relaxation processes and they precess producing radio signals proportional to the magnitude of their initial alignment. Contrast between nuclei develops as a result of the different relaxation rates at which each nuclei realigns with the magnetic field. The positions of the nuclei are localized by the application of spatially dependent magnetic fields called gradients. The radio signals produced by the processing nuclei are measured or "read out" after a predetermined time has elapsed from the initial RF excitation. The acquired signals are processed by means of the Fourier Transform into MR image data. See R. R. Edelman et al., Clinical Magnetic Resonance Imaging, W. B. Saunders (USA) (1990)(hereafter CMRI), incorporated herein by reference.
There are two important requirements for MRA which distinguish it from other MRI applications. First, high resolution is necessary in MRA in order to detail fine vascular anatomy. Second, high contrast is required in order to separate regions of flow from regions of stationary tissue.
The raw MR image data set, often referred to as "K space" is commonly parameterized by a quantity "K", which has dimensions of "cycles/centimeter", and which is related to the spatial parameter measured in "centimeters" through the Fourier Transform. The modern conceptualization of the MR imaging experiment is that the object to be imaged is directly sampled in its "K space" representation. See B. Twieg, The K-Space Trajectory Formulation Of The NMR Imaging Process With Applications In Analysis And Synthesis Of Imaging Methods, Medical Physics, Vol. 5, pp. 140-51 (1983). All characteristics of the digital sampling of K-space determine the sampling issues in image space. For example, the effective resolutions in the image-space and K-space are identical, as are the dimension of the acquisition, 2DFT versus 3DFT. On standard clinical imagers, 3DFT acquisitions offers higher spatial resolution in the slice direction than 2DFT imaging. Because resolution is essential to good quality MR images, 3DFT techniques in general enjoy an advantage over 2DFT methods for MRA.
Although conventional MR images will occasionally demonstrate striking contrast between blood vessels and background, producing an angiograph like image, in general, MR images obtained by standard two-dimensional Fourier transform (2DFT) methods are not well suited for angiography. MRA is a family of methods in which MR data is collected and computer processed in order to produce images resembling conventional x-ray angiograms. All methods require some way to generate contrast between flowing blood and stationary tissue. Prior MRA methods can be broadly divided into "white blood" and "black blood" techniques.
In "white blood" methods, signal from flowing blood is optimized while signal from stationary blood is suppressed. In "black blood" methods, signal from flowing blood is suppressed while signal from stationary blood is optimized. In other words, flowing blood is made to appear dark or black in black blood images and bright or white in white blood images. For a more complete discussion of MRA, see Listerud, J., First Principles of Magnetic Resonance Angiography, Magnetic Resonance Quarterly, Vol. 7, No. 2, pp. 136-170 (1991)(Listerud), incorporated herein by reference.
In standard MRI, two types of tuned RF signals have been suggested for perturbing nuclei, namely spin echo sequences and gradient echo sequences. Generally, a spin echo sequence is a pulse signal wherein an initial 90.degree. pulse is transmitted followed at a prescribed time by a 180.degree. pulse. The 90.degree. pulse excites the protons producing an initial free induction decay (FID) signal. It will be understood that the FID signal is not directly used for imaging, but rather, an echo of the FID signal is used. The 180.degree. pulse refocuses the transverse magnetization so that dephasing effects are cancelled at the time of the echo. The time period between 90.degree. pulses is referred to as the repetition time (TR). A gradient echo sequence is a pulse sequence having an initial pulse, which is not necessarily 90.degree. and is referred to as an alpha pulse to denote its variability. The echo is formed by a gradient manipulation and not by a 180.degree. pulse. Consequently, the TR interval can be reduced significantly preserving good signal to noise.
Edelman reports that the generation of black blood angiographs using a combination of pre-saturation pulses, gradient echo pulses and so-called spoiler pulses gave very low contrast. RR Edelman, et al., Extracranial carotid arteries: Evaluation with "Black Blood" Angiography, Radiology, Vol. 177, pp. 45-50 (1990). One of the previous advantages of using gradient echo pulse sequences in MRA is the reduction in time required to generate a complete image, as compared to a spin echo sequence, especially when acquiring a three dimensional (3D) Fourier transform data set. For example, CMRI reports that TR for spin echo sequences cannot be reduced much below 200 msec. Imaging time for 3D Fourier transform spin echo data was regarded as prohibitive, on the order of one hour or more. However, spin echo sequences produce greater "Black Blood" contrast than gradient echo sequences.
Consequently, a need exists for methods which result in the production of non-invasively obtained angiographs by using MRI techniques, i.e. without the need for the administration of exogenous agents, and which provides greater resolution and shorter imaging times than those MRA methods presently employed.
The present invention resolves the above problems through the use of so-called fast spin echo sequences. Through the use of this technique, not only is greater Black Blood resolution possible, but also, the need for presaturation pulses and spoiler pulses is reduced. Although fast spin echo sequences have been known in the past, their use has been largely ignored because image quality has been inadequate. However, this sequence has been reported as being implemented recently on a 1.5T SIGNA, GE Medical Systems. The generation of black blood angiographs using fast spin echo sequences has not been reported and such use and adaptation forms the basis of the novel nature of the invention.